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颞叶癫痫慢性模型中CA1和齿状回病理生理改变的区域异质性。

Regional heterogeneity of pathophysiological alterations in CA1 and dentate gyrus in a chronic model of temporal lobe epilepsy.

作者信息

Rempe D A, Mangan P S, Lothman E W

机构信息

Department of Neurology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.

出版信息

J Neurophysiol. 1995 Aug;74(2):816-28. doi: 10.1152/jn.1995.74.2.816.

DOI:10.1152/jn.1995.74.2.816
PMID:7472385
Abstract
  1. Extracellular and intracellular recording techniques were employed in brain slice preparations to characterize responses of hippocampal tissue in the post-self sustaining limbic status epilepticus (post-SSLSE) model of chronic temporal lobe epilepsy (TLE) as compared with responses in slices from control animals. Experiments were performed > or = 1 mo, and up to 7 mo, after status epilepticus. Two regions of the hippocampal formation linked to different aspects of epileptogenesis, the CA1 region and the dentate gyrus (DG), were studied. In any given experiment, CA1 and DG were examined in different slices from the same animal. 2. Pyramidal cells in CA1 were activated by means of electrodes positioned over fiber bundles that monosynaptically project to these cells, either those located in the stratum lacunosum/moleculare or those in the stratum radiatum. Granule cells were similarly activated by electrodes positioned in the perforant path. Full input-output curves were determined by varying stimulus strength and charting the amplitudes of population spikes (PSs). 3. Two indexes, stimulus sensitivity and responsiveness, were quantified in control tissue and in post-SSLSE tissue by means of input-output curves to provide comparisons between normal and epileptic tissue. There were no changes in stimulus sensitivity, defined as the stimulus intensity required to evoke comparable responses in input-output curves, between control and post-SSLSE tissue. However, responsiveness, defined as the number of extracellular PSs or intracellular action potentials (APs) elicited by a stimulus strength giving rise to maximal-amplitude PSs, proved a reliable method for identifying and categorizing epileptic responses. This index allowed for comparisons between anatomic regions within an experiment as well as among experiments for the same region. Both CA1 pyramidal cells and DG granule cells from post-SSLSE tissue showed hyperresponsiveness relative to control tissue. 4. Control tissue never exhibited > 2 PSs in either CA1 or DG in response to stimuli that produced maximal-amplitude PSs. Therefore a criterion of > or = 3 PSs was adopted to delineate tissue as hyperresponsive on the basis of extracellular responses. In CA1 about one half of the post-SSLSE slices displayed > or = 3 PSs with stimuli giving maximal-amplitude PSs, meeting the criterion for hyperresponsiveness; in DG about one fifth of the slices showed hyperresponsiveness. 5. CA1 and DG differed with respect to the spectrum of hyperresponsiveness they exhibited, this being more robust in CA1. The two regions studied also showed heterogeneity with respect to maximal PS amplitudes.(ABSTRACT TRUNCATED AT 400 WORDS)
摘要
  1. 采用细胞外和细胞内记录技术,在脑片标本中对慢性颞叶癫痫(TLE)的自维持性边缘性癫痫持续状态后(post-SSLSE)模型的海马组织反应进行特征描述,并与对照动物脑片的反应作比较。实验在癫痫持续状态后1个月及以上、最长7个月进行。研究了海马结构中与癫痫发生不同方面相关的两个区域,即CA1区和齿状回(DG)。在任何给定实验中,CA1和DG在来自同一动物的不同脑片中进行检测。2. CA1区的锥体细胞通过置于纤维束上方的电极激活,这些纤维束单突触投射至这些细胞,这些纤维束位于腔隙/分子层或放射层。颗粒细胞通过置于穿通通路的电极同样被激活。通过改变刺激强度并绘制群体峰电位(PS)的幅度来确定完整的输入-输出曲线。3. 通过输入-输出曲线在对照组织和post-SSLSE组织中对刺激敏感性和反应性这两个指标进行量化,以比较正常组织和癫痫组织。刺激敏感性定义为在输入-输出曲线中引发可比反应所需的刺激强度,对照组织和post-SSLSE组织之间无变化。然而,反应性定义为由产生最大幅度PS的刺激强度引发的细胞外PS或细胞内动作电位(AP)的数量,是识别和分类癫痫反应的可靠方法。该指标允许在实验内的解剖区域之间以及同一区域的不同实验之间进行比较。来自post-SSLSE组织的CA1锥体细胞和DG颗粒细胞相对于对照组织均表现出反应过度。4. 对照组织在CA1或DG中对产生最大幅度PS的刺激反应时,从未出现超过2个PS。因此,采用≥3个PS的标准,根据细胞外反应将组织界定为反应过度。在CA1,约一半的post-SSLSE脑片在给予最大幅度PS的刺激时显示≥3个PS,符合反应过度的标准;在DG,约五分之一的脑片显示反应过度。5. CA1和DG在它们表现出的反应过度谱方面存在差异,CA1更为明显。所研究的这两个区域在最大PS幅度方面也表现出异质性。(摘要截短至400字)

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